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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1346-1352. Prepublished online as a Blood First Edition Paper on April 25, 2006; DOI 10.1182/blood-2005-12-007971. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2005-12-007971v1 108/4/1346    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Menoret, E. Articles by Pellat-Deceunynck, C. Search for Related Content PubMed PubMed Citation Articles by Menoret, E. Articles by Pellat-Deceunynck, C. Related Collections Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Mcl-1L cleavage is involved in TRAIL-R1– and TRAIL-R2–mediated apoptosis induced by HGS-ETR1 and HGS-ETR2 human mAbs in myeloma cells Emmanuelle Menoret, Patricia Gomez-Bougie, Alexandrine Geffroy-Luseau, Sylvanne Daniels, Philippe Moreau, Steven Le Gouill, Jean-Luc Harousseau, Regis Bataille, Martine Amiot, and Catherine Pellat-Deceunynck From Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 601 (U601), Nantes, France; Université de Nantes, Nantes Atlantique Universités, Nantes, France; Centre Hospitalo-Universitaire (CHU), Service d'Hématologie Clinique, Nantes, France; and Centre de Lutte Contre le Cancer Nantes Atlantique, Saint-Herblain, France. We evaluated the ability of 2 human mAbs directed against TRAILR1 (HGS-ETR1) and TRAILR2 (HGS-ETR2) to kill human myeloma cells. HGS-ETR1 and HGS-ETR2 mAbs killed 15 and 9 human myeloma cell lines (HMCLs; n = 22), respectively. IL-6, the major survival and growth factor for these HMCLs, did not prevent their killing. Killing induced by either HGS-ETR1 or HGS-ETR2 was correlated with the cleavage of Mcl-1L, a major molecule for myeloma survival. Mcl-1L cleavage and anti-TRAILR HMCL killing were dependent on caspase activation. Kinetic studies showed that Mcl-1L cleavage occurred very early (less than 1 hour) and became drastic once caspase 3 was activated. Our data showed that both the extrinsic (caspase 8, Bid) and the intrinsic (caspase 9) pathways are activated by anti–TRAIL mAb. Finally, we showed that the HGS-ETR1 and, to a lesser extent, the HGS-ETR2 mAbs were able to induce the killing of primary myeloma cells. Of note, HGS-ETR1 mAb was able to induce the death of medullary and extramedullary myeloma cells collected from patients at relapse. Taken together, our data clearly encourage clinical trials of anti–TRAILR1 mAb in multiple myeloma, especially for patients whose disease is in relapse, at the time of drug resistance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Ashkenazi, P. Holland, and S. G. Eckhardt Ligand-Based Targeting of Apoptosis in Cancer: The Potential of Recombinant Human Apoptosis Ligand 2/Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (rhApo2L/TRAIL) J. Clin. Oncol., July 20, 2008; 26(21): 3621 - 3630. [Abstract] [Full Text] [PDF] A. Geffroy-Luseau, G. Jego, R. Bataille, L. Campion, and C. Pellat-Deceunynck Osteoclasts support the survival of human plasma cells in vitro Int. Immunol., June 1, 2008; 20(6): 775 - 782. [Abstract] [Full Text] [PDF] M. Romagnoli, G. Desplanques, S. Maiga, S. Legouill, M. Dreano, R. Bataille, and S. Barille-Nion Canonical Nuclear Factor {kappa}B Pathway Inhibition Blocks Myeloma Cell Growth and Induces Apoptosis in Strong Synergy with TRAIL Clin. Cancer Res., October 15, 2007; 13(20): 6010 - 6018. [Abstract] [Full Text] [PDF]

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